The lab is interested in understanding molecular and cellular mechanisms underlying synapse formation and synaptic plasticity, and in the long term elucidating synaptic mechanisms underlying neuronal circuit function in animal behavior. We believe that these studies will provide fundamental insights into neural underpinnings for learning and memory, and will identify synaptic and neural circuit malfunctions that are involved in many neurological and mental disorders, such as Alzheimer's disease, depression and autism disorders. Specifically, during the 2014 fiscal year, we have made following progress: For research Aim 1: we have successfully determined the role of GSG1L, a tetraspanning protein that binds to AMPARs in the regulation of excitatory synaptic strength and animal behavior with a combination of electrophysiological, molecular and cellular biological, genetic and behavioral approaches. We found that GSG1L plays a unique and critical role in the negative regulation of AMPAR-mediated synaptic transmission. In addition, GSG1L plays a distinct role in the modulation of AMPAR gating. Finally, we found that the cellular function of GSG1L is important for neural circuit function that underlies object recognition memory in animals. Currently a manuscript for this work has been submitted to a major neuroscience journal for publication. For research Aim 2: we have revealed several key molecular processes that are critical for the development of inhibitory synapses. We found that activities of glutamate receptors in developing neurons are crucial for inhibitory synapse development. Current a manuscript for this work has been submitted for publication. For research Aim 3, we have determined that excitatory synaptic transmission onto principle neurons in the hippocampus is crucial for the maintenance of neuronal inhibition. Specifically, we found that the maintenance of inhibitory inputs originated from Somatostatin-positive, but not Parvalbumin-positive interneurons are sensitive to ongoing excitatory input. Currently we are performing electrophysiological and morphological assays to further characterize the phenomena. For research Aim 4, we have made significant progress to determine the role of glutamatergic input onto midbrain dopamine neurons. During the 2014 fiscal year, we have systematically performed immunohistochemical and electrophysiological experiments to characterize transgenic/conditional knockout mice in which the majority of glutamatergic input onto midbrain dopamine neurons has been genetically inactivated. Ongoing behavioral studies demonstrate that while glutamatergic input contributes to burst firing of dopamine neurons, it plays an insignificant role in a variety of rewarding behaviors. Currently, we are testing several different rewarding behaviors with these mice, such as conditioned place preference and cocaine-mediated behavioral sensitization. Finally, during the 2014 fiscal year, we have collaborated with Dr. Katherine Roche group at NINDS, NIH to study AMPA receptor trafficking, which resulted in one publication. In addition, we collaborated with Dr. Kent Hamras lab at the University of Texas Southwestern Medical Center in Dallas to generate GSG1L knockout rats to study the role of GSG1L in the regulation of synaptic transmission and animal behavior, which has resulted in a manuscript submitted for publication.